The metabolism of pyridine nucleotides in intact human erythrocytes will be investigated with particular attention to the possible relationship that these compounds may have to membrane transport and permeability. These nucleotides may describe the metabolic status of the human red cell in a unique manner and may thereby reflect special metabolic relationships to physiological processes which cannot be uncovered by traditional procedures. The mammalian red cell seems to be especially suited for these studies because of its relatively simple metabolism; compared to more typical cells, the number of reactions with which pyridine nucleotides are involved are limited. Specifically, (1) redox and phosphorylation states will be evaluated as a function of pH, (2) the metabolism of the anaerobic erythrocyte will be described, and (3) the role of NADPH in passive movement of potassium across the cell membrane will be examined, in normal and abnormal erythrocytes. The basis for hemolysis in primaquine-sensitive disease may be related to faulty NADPH metabolism.